This invention relates to the chemoprophylaxis of disease caused by DNA and RNA viruses. More particularly it relates to a method of treating a virus-infected host with a class of chemical compounds at extremely low dosages in the order of about 250 picograms (10.sup..sup.-12 grams; pg) to 250 micrograms (10.sup..sup.-6 grams; .mu.g) per kilogram of host body weight. The difference between a picogram and a milligram is the same as the difference between one and one billion.
The compounds which are active in the practice of the present invention are those having a stereochemically unencumbered access to a nitrogen-nitrogen bond. The compounds within the purview of the invention are exemplified by those having the following formula: ##STR1## where R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are selected from the class consisting of hydrogen, lower alkyl, aryl, heterocyclic aryl, COR.sup.5, CSR.sup.5, CONHR.sup.5, SO.sub.2 R.sup.5 where R.sup.5 is lower alkyl, aryl, heterocyclic aryl, amino, lower alkoxy and adamantyl, with the proviso that R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4 are different where R.sup.1 or R.sup.3 is COR.sup.5, CSR.sup.5, CONHR.sup.5 or SO.sub.2 R.sup.5. R.sup.1 and R.sup.2 or R.sup.3 and R.sup.4 or R.sup.1 and R.sup.3 when taken together may be selected from the class consisting of substituted alkylidene and substituted azo. R.sup.3 and R.sup.4 taken together may be substituted alkylidene. R.sup.2 and R.sup.4 may be a valence bond between the two nitrogens. As used herein the terms lower alkyl, lower alkoxy and the like define groups having 1 to about 6 carbons.
One of the problems in the field of virology has been the absence of predictability in chemoprophylaxis. Indeed, there had existed a belief among some authorities that chemoprophylaxis would not be successful in the treatment of virus infections. Up to the present time there has been no predictability with regard to the antiviral effect of particular compounds with the exception of certain compounds known to induce interferon. A compound may not be active while its homolog or a substituent is quite active. An indicated activity is frequently not reproducible with the same compound in the same dosage.
In the entire field of virology, only three compounds have been made commercially available that have antiviral effects in humans and all of these have been effective against a limited group of viruses. One of them is a compound for the treatment of kerotitis due to Herpes simplex virus. Another is a compound effective against particular strains of Influenza, and the third is a compound effective in the chemoprophylaxis of smallpox and some of the complications of vaccination.
The exact requirements for a successful antiviral compound have not been determined. Besides the chemical nature of the compound, other factors that may be involved are solubility, permeability, particle size and the like. It has been suggested that a successful antiviral agent may not attack a virus directly but rather may stimulate factors of host resistance. An effective chemoprophylactic compound is one which would have effect against a broad spectrum of virus-induced diseases, and would be effective in oral administration. Ideally, the chemoprophylactic nature of the compound should be identifiable with a particular portion of its chemical molecule and be modifiable by substituents added to the basic molecule portion. Also the therapeutic index should preferably be large, over about 100. The therapeutic index is the ratio of an acute toxic dose to an effective dose in a given host. No compound is known up to the present time which meets the ideal.